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Tesi etd-03292018-084631


Tipo di tesi
Tesi di dottorato di ricerca
Autore
SIMI, GIOVANNA
URN
etd-03292018-084631
Titolo
CANCER&PREMATURE OVARIAN FAILURE: NEW STRATEGIES TO PREVENT OVARIAN LOSS DURING CHEMOTHERAPY
Settore scientifico disciplinare
MED/40
Corso di studi
SCIENZE CLINICHE E TRASLAZIONALI
Relatori
tutor Prof. Gadducci, Angiolo
correlatore Prof. Artini, Paolo Giovanni
Parole chiave
  • cancer
  • fertility preservation
Data inizio appello
09/04/2018
Consultabilità
Non consultabile
Data di rilascio
09/04/2088
Riassunto
Cancer can be a devastating diagnosis. Despite the considerable advances done and the extensive knowledge acquired over time, it remains a major health problem with repercussions not only on a physical level, but also on the psychological and social spheres. Increases in the number of individuals diagnosed with cancer each year, due in large part to aging and growth of the population, as well as improving survival rates, have led to an ever-increasing number of “cancer survivors”. This denomination is used to describe any person who has been diagnosed with cancer, from the time of diagnosis through the balance of life. The goal of treatment is to ‘‘cure’’ the cancer, or prolong survival in patients with advanced disease, meanwhile preserving the highest possible quality of life in both the long and short term. Many survivors, even among those who are cancer free, must cope with the long-term effects of treatment, as well as psychological concerns such as fear of recurrence. Loss of fertility is one of the most devastating consequences of radio- or cytotoxic therapy for these young patients who, having overcome their disease, have expectations of a normal reproductive life. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. Fertility preservation and the ability to maintain future parenthood are issues that present and persist from the moment of a cancer diagnosis and they are essential components of a comprehensive approach to cancer treatment. In female cancer patient, various strategies have been used for fertility preservation. The combining use of GnRH agonist or oral contraceptive during chemotherapy is common but not so effective in order to protect ovary and fertility. To date, embryo cryopreservation is the only method widely used for fertility preservation. However, if it is not allowed or not available both oocyte cryopreservation and ovarian tissue banking followed by tissue transplant have also been successful. Each approach has associated advantages and disadvantages relating to current success rate, required delay in cancer treatment, sperm requirement, and risk of reintroducing cancer cells.
chemotherapy and infertility
The ovary is susceptible to chemotherapy-induced damage, particularly following treatment with alkylating agents such as cyclophosphamide. Ovarian damage is drug and dose-dependent and it’s related to age at the time of treatment, with progressively smaller doses required to produce ovarian failure with increasing age. The effect of chemotherapy on the ovary is not an “all or nothing” phenomenon and the number of surviving primordial follicles following exposure to chemotherapy correlates inversely with the dose of chemotherapy and the nature of agent. Histological studies of human ovaries have shown chemotherapy to cause ovarian atrophy and global loss of primordial follicles. A few human and animal studies have demonstrated that chemotherapy induces damage to ovarian pre-granulosa cells and that apoptosis occurs during oocyte and follicle loss. In addition, injury blood vessels and focal fibrosis of the ovarian cortex are further patterns of ovarian damage caused by chemotherapy.
Study in animals show that the loss of inhibitory influence of small growing follicle on initiation of primordial follicle growth will result in increased activation of the resting pool of primordial follicles which will be further destroyed by chemotherapy.
Recent studies have demonstrated that the aqueous extract of saffron (SE), rich in carotenoids, has antitumor effects and radical scavenger properties. By virtue of its antioxidant properties, we propose herein a possible role of SE in protecting ovary from chemotoxic effects in a mouse model.
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